In this renewal proposal, the Washington University Mass Spectrometry Facility plans to establish a regional Biotechnology Mass Spectrometry Resource to serve the nine state region centered around Missouri, plus a national Resource for isotope ratio monitoring gas chromatography/mass spectrometry (GC/MS). There are five major objectives for this Resource: 1. To provide facilities and technical support to NIH-supported investigators requiring mass spectrometric analyses, for the states of Missouri, Illinois, Iowa, Nebraska, Kansas, Oklahoma, Arkansas, Tennessee, and Kentucky. 2. To develop new and improved methods for determining metabolic turnover rates in humans using stable isotope tracers. An isotope ratio monitoring GC/MS system will be developed, which will be open to qualified investigators at the national level. 3. To improve the precision and reliability of quantitative assays, with particular emphasis on compounds present in small quantities, stable isotope tracers, and multiple assays during a single anslysis. 4. To automate the collection and analysis of mass spectrometer data with computers, to increase the reliability of the assays and the effective use time of the instrument. 5. To develop clinically significant assays, in collaboration with our medical users. Investigators at the Resource will use GC/MS with electron impact ionization and positive and negative chemical ionization, to study enzyme kinetics, the polysaccharide sequence of glycoproteins, the structures of SRS-A, fungal toxins, synthetic steroid inhibitors, and photo-crosslinked phospholipids, the metabolism of amino acids and proteins in humans, the role of prostaglandins in the control of renal blood flow, the efficacy of tricyclic antidepressants in treating depression, the metabolism and physiology of inositols, the pharmacokinetics of anticonvulsants and sedatives, and biochemical lesions causing inborn errors of metabolism.